This invention relates to a method for inducing bone growth, and a method for screening porous structures for their respective osteoinductive or osteoconductive potentials.
In recent years, interest has been shown in the osteoconductive properties of a porous hydroxyapatite substratum that is obtained after hydrothermal conversion of the calcium carbonate exoskeletal microstructure of the scleractinian reef-building corals, Porites and Goniopora. This hydroxyapatite is characterized by a relatively uniform network of interconnected channels and pores, similar to the mineralized inorganic supporting structure of living bone. Experimental evidence has established the osteoconductive properties of the porous substratum when it is implanted in orthotopic sites, and the material has been used experimentally in reconstructive operations, particularly craniofacial procedures, as an alternative to autogenous bone grafts. Studies heretofore have shown that implantation in extraskeletal sites in dogs and rodents results in penetration of fibrovascular tissue, without bone formation, which indicated that the porous hydroxyapatite does not act as a bone-inducing substratum in those animals and that ingrowth of bone within the three dimensional framework depends on close apposition of the implant with viable bone at the interfaces of the material.
However it has now surprisingly been shown that bone does form in porous hydroxyapatite that has been implanted extraskeletally in non-human primates. Details are provided in Example 1 below.
The applicant is further aware of evidence that the shape and configuration (hereinafter referred to as "the geometry") of the porous hydroxyapatite substratum can be a relevant factor in determining the osteoconductive potential of hydroxyapatite. Example 2 below describes in detail an investigation into geometric importance, and sets out the results of the investigation which lead to a conclusion that the geometry of a substratum can be critical for inducing bone growth. Thus it is conceivable that a variety of porous substances could conveniently be coated with hydroxyapatite or with other extracellular matrix components with binding affinity for osteogenin. (Osteogenin and related bone morphogenetic proteins (BMPs) are protein initiators that regulate cartilage and bone differentiation in vivo.) The applicant therefore foresees a need for a screening method whereby osteoconductive or osteoinductive potentials of various material and/or optimal geometry thereof can be tested.